%0 Journal Article
%A Larsson, Johan N. K.
%A Kumar, Ranjeet
%A Buratti, Fiamma Ayelen
%A Nyström, Sofie
%A Wittung-Stafshede, Pernilla
%A Hammarstrom, Per
%T Heat shock protein 10 as a chaperone modulating α‐synuclein amyloid fibril formation
%J Protein science
%V 35
%N 2
%@ 0961-8368
%C Hoboken, NJ
%I Wiley
%M PUBDB-2026-00754
%P e70452
%D 2026
%X HSP10 is a well-known human co-chaperone that interacts with HSP60 to comprise the HSP60/10 chaperonin complex which upholds mitochondrial proteostasis. HSP10 also demonstrates independent roles in binding to misfolded proteins and interacts with several amyloidogenic client proteins. Using a variety of biophysical and biochemical methods, we studied the interactions of HSP10 with the amyloidogenic protein α-synuclein (α-syn) associated with Parkinson's disease. HSP10 efficiently inhibited fibril formation of wild type (WT) and disease-mutant A30P α-syn at sufficient concentrations of chaperone by both binding to α-syn monomers and by blocking secondary nucleation on fibril surfaces. However, under sub-stoichiometric conditions, below 1:5 (HSP10:α-syn), the chaperone sequestered multiple A30P α-syn monomers and thereby promoted nucleation of fibril formation with a magnitude comparable to the efficacy of seeding with preformed fibrils. The fibril formation acceleration effect of the HSP10 chaperone was client-specific as it was observed for A30P but not WT α-syn. Our results broaden the scope of HSP10 chaperone activity and can have implications for disease onset in synucleinopathies.
%F PUB:(DE-HGF)16
%9 Journal Article
%R 10.1002/pro.70452
%U https://bib-pubdb1.desy.de/record/646209